SUMMARY OF THE PRIOR ART
It is known, from the article by Van Scott et al. in Arch. Dermatol., Vol. 110, October 1974, pages 586-590, to use a-hydroxylated acids in topical preparations in order to carry out a particularly effective keratolysis in the treatment of ichthyosis and of dry skins.
Likewise, Middleton has described, in J. Soc. Cosmet. Chem., 25 (1974), pages 519-534, a skin cream containing lactic acid or sodium lactate in order to reduce the dry skin forming scales in the corneal layer or stratum corneuln.
The use of .alpha.-hydroxylated acid derivatives, by topical use, for treating a dry skin associated with eczema has also been published by Malcolm W. Greaves in Cosmetics and Toiletries, Vol. 105, October 1990, pages 61-64. This article emphasises, on page 61, right-hand column, second last paragraph, that, like urea, .alpha.-hydroxylated acids have been restricted in use due to their irritant nature. This article relates to the use of a composition containing a methoxypropylgluconamide with a lower acidity. This compound is also the subject of European Patent Application EP-A-0,338,565 of Revlon. This European application relates to a compound of formula: ##STR1## in which formula p is an integer from 1 to 4, (C.sub.n H.sub.2n) is a straight- or branched-chain alkyl bridge in which n is an integer from 1 to 6, and (C.sub.m H.sub.2m-1) is a straight- or branched-chain alkyl group in which m is an integer from 1 to 6.
These compounds are therefore amide derivatives of an at least dihydroxylated acid necessarily containing an ether chain, which compounds are different from those developed and used in the context of the present invention.
Greaves et al. have observed that the compounds described in this document EP-A-0,338,565 have little effectiveness as keratolytic agents, hence the necessity to use them at very high concentrations. In addition, this keratolytic property cannot be modified as it is very similar from one product to another.
In contrast, in the context of the present invention, new compounds were able to be discovered whose activity can be modified from a very powerful activity to a much gentler activity.
The document EP-A-0,273,202, Van Scott et al., describes additives based on hydroxycarboxylic acid which promote the topical actions of therapeutic agents present in an amount ranging from 0.01 to 99 weight % of the total composition.
The .alpha.-hydroxylated acids, their salts and their lactone form described in the document EP-A-0,273,202 have a very strong keratolytic power when they are used at high concentrations and at acid pH values. However, under such conditions of use, they are poorly tolerated by the skin surface and cause stinging, red blotches and inflammatory phenomena, which greatly restricts their use under such conditions.
In the present invention, new products have been discovered which are non-irritant in a wide pH range which can range from a very acidic pH in the region of 3 or 3.5 to a neutral pH of the order of 7, even when they are tested at very high concentrations such as 100%.
Hydroxylated acid amides obtained with a monoamine or a diamine which can in particular contain a C.sub.1 -C.sub.8 alkyl radical are also known from the documents Van Scott U.S. Pat. Nos. 4,105,783 and 4,197,316. In the context of the invention, when it concerns amides, the latter are obtained with a monoamine having a C.sub.10 -C.sub.30 fatty alkyl radical.
The document Revlon EP-A-0,447,064 also relates to alkoxyamides of the type of those described in the above document EP-A-0,338,565 which are different from those developed and used in the context of the present invention.
Various other documents relate to esters of the hydroxylated acid acid functional group which are different from those developed and used in the context of the present invention. These documents relating to esters are WO-A-95/03032, EP-A-0,599,819 Van Scott, EP-A-0,273,202; EP-A-0,521,647 Unilever in which citric acid fatty acid esters are described in which the acid functional groups of the citric acid are necessarily substituted by ester bonds with an ester substitution group R.sub.1, R.sub.2 and R.sub.3. The hydroxyl functional group of the citric acid can be substituted by an acyl group R.sub.4 which is preferably an acyl group having from 2 to 4 carbon atoms. In the context of the invention, ester bonds on the acid group of the hydroxylated acid are not sought for and an ester bond from the hydroxyl functional group of the hydroxylated acid comprises at least 7 carbon atoms.
The application from l'Oreal EP-A-0,526,302 relates to 2,5-dihydroxybenzenecarboxylic acid salts or esters in which the esters are produced on the acid functional group which are different from those developed and used in the context of the present invention. Mention may be made, as other esters of the acid functional group of the hydroxylated acid, of the documents Unilever EP-A-0,282,289; EP-A-0,261,812; the document U.S. Pat. No. 5,302,377 of Croda; the document U.S. Pat. No. 4,078,147 Ukai; Swiss Patents CH-A-449,852 and 443,565 of the Laboratoires Prod'Hyg, French Patent Henkel FR-A-2,390,160; and the document Henkel DE-4,033,565.
Mention will further be made, as amide, of German document DE-A-1,543,929 which describes amides of 2,4-dihydroxy-3,3-dimethylbutyric acid from a C.sub.5 to C.sub.30 hydroxyalkylamine or alkoxyalkylamine, i.e. a different amine from the alkylamines of the invention having C.sub.10 -C.sub.30.
Moreover, topical compositions intended for skin treatment based on salicylic acid derivatives are also known from the document FR-A-2,581,542 of l'Oreal. These derivatives correspond to the formula: ##STR2## in which R represents a hydrocarbon chain which can have up to 17 carbon atoms and R' can represent a hydroxyl functional group or an ester functional group of the formula ##STR3## containing from 2 to 16 carbon atoms, it being possible for this chain to be saturated or unsaturated and for n to have a value between 0 and 14 (see the description and claim 1 in particular).
The preferred compounds are those in which R' denotes a hydroxyl functional group and R an alkyl group having from 3 to 11 carbon Atoms (claim 2 and page 3, lines 10 to 20).
It emerges from this formula that these derivatives are necessarily substituted in position 5 of the phenyl ring by a radical containing a ketone functional group which appears to be the determining factor in providing a keratolytic activity greater than that of salicylic acid, as indicated in the description on page 2, lines 5 to 10.
In the context of the present invention, new hydroxylated acid derivatives have been discovered which are particularly active and non-irritant, including salicylic acid derivatives other than derivatives substituted in position 5 of the phenyl ring of the salicylic acid which are described in this document.
In addition, it has been discovered that the derivatives of the invention also exhibited a significant emulsifying power which makes it possible to use them as the sole emulsifying agent, that is to say used alone, or as a coemulsifying agent, making it possible to reduce the amount of other emulsifying agents.
Moreover, the 5-keto-substituted derivatives of salicylic acid described in the above document FR-A-2,581,542 have the major disadvantage that the ketone bond cannot be hydrolyzed enzymatically. In addition, although an ester functional group is provided on the hydroxyl functional group, the only derivative prepared is the acetyl ester in Preparation Example G which appears, from the pharmacology tests of Tables I and II, to be less active than the free derivatives.
In fact, this document FR-A-2,581,542 teaches those skilled in the art the necessity of using derivatives substituted in position 5 of the salicylic acid by a ketone bond and the fact that the hydroxyl functional group of the salicyclic acid must be free.
This is confirmed by the document FR-A-2,607,498 of l'oreal which relates to lipophilic quaternary ammonium salicylates in which the hydroxyl functional group of the salicylic acid is unsubstituted and which always contains, in position 5, the radical bonded by a ketone bond to the phenyl ring, this salicylate being in the ionic form by virtue of the presence of a quaternary ammonium which comes to be coupled to the COO.sup.- functional group of the acid. Consequently, these documents dissuade those skilled in the art from searching for salicylic acid derivatives other than the 5-keto-substituted derivatives, that is to say carrying a radical bonded by a ketone bond.
These compounds, however, have the disadvantage that they are not hydrolyzable, either spontaneously or under the action of skin or bacterial enzymes.
Document EP-A-0,378,936 also uses the same salicylic acid derivatives to carry out skin ageing treatment, which derivatives have the same disadvantages of not being hydrolyzable, either spontaneously or under the action of skin or bacterial enzymes.
Moreover, the document EP-A-0,433,104 of Unilever relates to a shampoo composition containing 2-hydroxyalkanoic acid in combination with a buffering agent forming a coacid, so that the pH of the composition is preferably between 3 and 5.
Further, the document EP-A-0,413,528 of Yu and Van Scott relates to amphoteric compositions and to polymer forms of .alpha.-hydroxy acid and to their therapeutic use in treating dry skins, acne, keratosis, psoriasis, eczema, ageing blotches, wrinkles, pallid skin, hyperpigmented skin, hyperkeratinized skin, inflammatory dermatoses or skin changes associated with age and as skin-cleaning product. In fact, as emerges from the list given on pages 29 and 30, it concerns the same hydroxy acids as those which are described in the document EP-A-0,273,202 analyzed above. These products are poorly tolerated by the skin surface and cause stinging, red blotches and inflammatory phenomena which greatly restrict their use.
A similar document further consists of the document EP-A-0,508,324 filed by Yu and Van Scott for treating signs of ageing of the skin, of the nails and of the hair.
Finally, the document EP-A-0,585,170 is also a l'Oreal document relating to a composition for treating acne containing the quaternary ammonium salt of the 5-ketone derivative of salicylic acid with a quaternary ammonium ion, encapsulated in liposome-type vesicles.
It is thus observed that the prior art demonstrates that intensive research is being carried out regarding the use of .alpha.-hydroxylated acids in cosmetic or pharmaceutical compositions but that none of the solutions proposed has been capable of simultaneously solving the problem of tolerance of these products by the skin surface, the acids being too harmful, and the problem of their modifiable effectiveness, as well as of their biocompatibility in being degradable or hydrolyzable spontaneously or under the action of skin or bacterial enzymes. In addition, their affinity with respect to lipid constituents of the epidermis remains limited.